Two parallel projects will be continued: 1) The influence of nucleic acid fine structure on the fidelity of DNA synthesis. 2) The elucidation of the biochemical basis of various mutator genes in E. coli. The first project involves the use of nucleotide analogues to determine what influence they have on the stability of DNA and how they are handled by several different DNA polymerases. The second project involves the preparation of extracts from isogenic strains of E. coli harboring various mutator genes and comparing their replication apparatus to the wild-type parent.